Role of KDEL receptor-dependent signaling in modulating of the cytoskeleton, molecular motors and their effect on the lysosomal distribution

Tapia Diego; Zamora Constanza; Guzman, Fanny; Arriagada, Gloria; Cancino, Jorge

Abstract

Introduction: Recently, a “new face” of the Golgi Complex (GC) has been revealed: its ability to generate signaling. The KDEL receptor- (KDELR) dependent signaling modulates the transport machinery to control anterograde and retrograde transport from the GC. Particularly striking is that acute stimulation of R-KDEL induces a rapid relocation of lysosomal organelles to the perinuclear area neighboring the AG, as well as, regulates the expression and posttranslational modifications of a significant number of actin and microtubule cytoskeleton proteins. Our findings lead us to propose the following hypothesis “the signaling generated by KDELR, modulates the lysosomal distribution through the actin and/or microtubules cytoskeleton”. Material and Methods: Human cells, cell microinjection, quantitative fluorescence image, gene expression, shRNA, drugs. Results: Transient KDELR stimulation not only modulates several signaling molecules involved on to control lysosomal function and increases the number of lysosome-related organelles; also induce the lysosomal relocation using molecular motors of actin and microtubules. Discussion KDELR-dependent signaling can be considered a regulatory system for cellular homeostasis by controlling lysosomal-related organelles biogenesis and function. Furthermore the lysosomes have an essential role on autophagy, where the lysosomal relocation is very important to autolysosome formation. The expected results will help to elucidate the mechanism through wish the signaling of KDELR induce the lysosomal movements using cytoskeleton and its relevance on therapeutic purposes of neurodegenerative diseases.

Más información

Fecha de publicación: 2016
Año de Inicio/Término: 2 al 6 de Noviembre
Financiamiento/Sponsor: Jorge Cancino